Whereas primate rod and cone photoreceptor outer segments exhibit differences in overall morphology, spectral sensitivity, membrane renewal, and susceptibility to degeneration in various diseases and retinal detachment, relatively little is known concerning organizational of molecular substructural differences between the outer segment membranes of these two photoreceptor types. In contrast to the case for rods, the structural relationship between vertebrate cone outer segment disc membranes and the enveloping plasma membrane remains uncertain, especially in primates. It has generally been assumed that most, if not all, of the discs in mammalian cones are continuous with the plasma membrane, but that many of the connections may be extremely small. However, the presence of small openings remains enigmatic. Even less is known about the functional dimensions and charge properties of those discs which are continuous with the plasma membrane or about the precise topographical distributions of cone outer segment membrane-specific molecules. Recent studies in our laboratory have demonstrated significant regional variations in primate cone outer segment membrane organization and molecular substructure. The major aim of the proposed study is to further define ultrastructural and immunocytochemical properties of primate cone photoreceptor cell membranes using a variety of conventional and recently developed electron microscopic techniques, including rapid-freezing, freeze substitution, deep-etching, freeze-fracture-labeling and label-fracturing. The proposed studies will investigate the extent to which cone disc membranes are continuous with the cone outer segment plasma membrane, the distribution and density of cone intramembrane particles, the presence of junctional complexes between cone outer segment and pigmented epithelial cell membranes, and the binding of cone-specific lectin and antibody probes to membrane-associated molecules of cone disc and plasma membranes. Regional differences in these properties will be evaluated by comparing results from foveolar, macular and peripheal regions of the fundus. These studies will add to our understanding of the dynamic functions of cone photoreceptors and may provide information important in future analyses of membrane morphogenesis, maintenance, and turnover as well al iodopsin-mediated phototransduction. It is hoped that these studies of normal photoreceptor substructure will also aid in the evaluation of early pathological changes in human and animal cone photoreceptors undergoing degeneration.